Clinical diagnostic instruments are those used to measure the presence and quantity of analytes in human blood, serum and other fluids. Examples of analytes that are measured include, but are not limited to, sodium, potassium, calcium, chloride, other electrolytes, glucose, lactate, cholesterol, lipids (e.g., triglycerides), and uric acid. In addition, the instruments are used to measure pH and concentrations of dissolved gases in these fluids. Many other analytes and attributes are also measured by these instruments. Theories identifying new physical and chemical characteristics which are indicators of the state of human health are frequently discovered, and analytical techniques for these new attributes are developed for use on these instruments. The actual component of the instrument which determines the concentration of the analyte of interest is often referred to as the electrode or sensor. Typically the analyte measurement system for these sensors is electrochemical, but could also be optical or could involve measurement of another physical or chemical property. The sensor may at times be complex and combine several systems. For example, an enzyme might be linked to the sensor matrix and catalyze the decomposition of an analyte, generating a component which can then be measured.
The successful measurement of an analyte depends on the interaction of instrument, sensor and reagents. The reagents are particularly important because they can impact the performance of both the sensor and instrument. Some of the reagents necessary for running the analyses on the clinical diagnostic instruments include the calibrators (reagents which have been formulated to contain a specified concentration of the analyte of interest, so that the assay can be run with said calibrator to fix a given response point for the instrument for this concentration), control products (products which are run along with analytical samples to determine if the assay is working properly), and analytical reagents (which include buffers, chemical reactants, etc.) which cause the chemical or physical reaction to occur with the analyte. Other reagents include wash solutions to clean test samples from the instrument. Some of these reagents are formulated in environments that include or simulate the environment of the component being measured. (E.g., some may be formulated in serum at a particular ionic strength and a particular pH. Others may have a particular lipophilic content.) These reagents are the same types of reagents used for manual assays, and, therefore, even though the discussion herein concentrates on reagents for clinical diagnostic instruments, including those that are automated, the same also applies to manual analytical techniques.
Many of the above reagents are formulated with preservatives, in order to extend their shelf life, since the reagents contain nutrients that will support microbial growth. This application deals with the efficacy of a mixed preservative system which has been unexpectedly found to be enhanced in performance when a particular buffer, imidazole or a derivative thereof, is used in the formulation. It also deals with how these buffers and a particular surfactant, BRIJ 700, enhance the precision and accuracy of enzyme biosensors.